OBJECTIVE: To investigate the frequency and characteristics of hprt- mutant T lymphocytes in the peripheral blood and synovium of rheumatoid arthritis (RA) patients compared with controls, and to correlate these findings with disease parameters. METHODS: An hprt- T cell assay was performed on blood and synovial samples from 93 RA patients, 8 osteoarthritis (OA) patients, and 19 control subjects. T cell clones were studied by flow cytometry and evaluated for fibronectin adhesion. RESULTS: RA patients showed a 5-fold increase in the frequency of mutant T cells in the peripheral blood compared with that in control peripheral blood, and a further 10-fold increase in the mutant T cell frequency in synovial tissue. In OA patients, the synovium also had a significantly higher frequency of hprt- mutant T cells compared with the peripheral blood, but at a lower level than in the rheumatoid synovium. RA peripheral blood mutant T cell clones displayed elevated fibronectin adhesion and beta1 integrin expression, similar to that observed in the RA synovial T cell lines. CONCLUSION: The origin of the mutated T cells in the peripheral blood of these patients appears to be the inflamed synovium of RA, and to a lesser extent, of OA, where the cells are exposed to a mitogenic and genotoxic environment.
OBJECTIVE: To investigate the frequency and characteristics of hprt- mutant T lymphocytes in the peripheral blood and synovium of rheumatoid arthritis (RA) patients compared with controls, and to correlate these findings with disease parameters. METHODS: An hprt- T cell assay was performed on blood and synovial samples from 93 RApatients, 8 osteoarthritis (OA) patients, and 19 control subjects. T cell clones were studied by flow cytometry and evaluated for fibronectin adhesion. RESULTS:RApatients showed a 5-fold increase in the frequency of mutant T cells in the peripheral blood compared with that in control peripheral blood, and a further 10-fold increase in the mutant T cell frequency in synovial tissue. In OA patients, the synovium also had a significantly higher frequency of hprt- mutant T cells compared with the peripheral blood, but at a lower level than in the rheumatoid synovium. RA peripheral blood mutant T cell clones displayed elevated fibronectin adhesion and beta1 integrin expression, similar to that observed in the RA synovial T cell lines. CONCLUSION: The origin of the mutated T cells in the peripheral blood of these patients appears to be the inflamed synovium of RA, and to a lesser extent, of OA, where the cells are exposed to a mitogenic and genotoxic environment.
Authors: Cindy L Zuleger; Michael D Macklin; Bret L Bostwick; Qinglin Pei; Michael A Newton; Mark R Albertini Journal: J Immunol Methods Date: 2010-12-21 Impact factor: 2.303
Authors: Noah A Kaitz; Cindy L Zuleger; Peng Yu; Michael A Newton; Richard J Albertini; Mark R Albertini Journal: Mutat Res Rev Mutat Res Date: 2022-03-11 Impact factor: 7.015
Authors: Yuji Yamanishi; David L Boyle; Sanna Rosengren; Douglas R Green; Nathan J Zvaifler; Gary S Firestein Journal: Proc Natl Acad Sci U S A Date: 2002-07-15 Impact factor: 11.205